Boc-D-N(Me)Leu-Leu-OH | 934715-73-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-D-N(Me)Leu-Leu-OH
• 英文别名: (2S)-4-methyl-2-[[(2R)-4-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoyl]amino]pentanoic acid
• CAS: 934715-73-8
• 化学式: C₁₈H₃₄N₂O₅
• 分子量: 358.478
• InChiKey: DOMCNVRMIWDDCA-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-D-N(Me)Leu-Leu-OH 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 生成 cyclo[D-N(Me)Leu-Leu-Val-Leu-Phe]
  参考文献：
  名称：

  Synthesis of Second-Generation Sansalvamide A Derivatives: Novel Templates as Potential Antitumor Agents

  摘要：

  We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.

  DOI：

  10.1021/jo061830j
• 作为产物：
  描述：

  D-亮氨酸 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 mineral oil 为溶剂， 反应 24.42h， 生成 Boc-D-N(Me)Leu-Leu-OH
  参考文献：
  名称：

  d-氨基酸位置影响Galaxamide类似物的抗癌活性：细胞凋亡机制研究。

  摘要：

  Galaxamide是一种来自Galaxaurafilosa的提取物，是一种含有五种l-亮氨酸的环状五肽。由于特殊的环状结构和优异的抗癌活性，Galaxamide及其类似物的合成及其后续的生物应用引起了极大的关注。在目前的工作中，我们通过用苯丙氨酸代替一个亮氨酸取代了一个L-亮氨酸，并改变了d-氨基酸的位置，从而合成了六个Galaxamide类似物。测试了合成的Galaxamide类似物对四种体外人类癌细胞系，人类肝细胞细胞（HepG2），人类乳腺癌细胞（MCF-7），人类乳腺癌细胞（MDA-MB-435）的抗癌作用。宫颈癌细胞系（Hela）。结果表明，具有不同d-氨基酸位置的Galaxamide类似物显示出独特的抗癌潜力。在位置5（Analog-6）上含有d-氨基酸的Galaxamide类似物具有最强的抗癌活性。机制研究表明，Analog-6可能通过抑制HepG2细胞在细胞周期亚G1期的

  DOI：

  10.3390/ijms18030544

文献信息

• Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines
  作者：Katerina Otrubova、Gerald Lushington、David Vander Velde、Kathleen L. McGuire、Shelli R. McAlpine

  DOI：10.1021/jm070731a

  日期：2008.2.1

  We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating, multiple drug-resistant colon cancers.
• Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
  作者：Robert P. Sellers、Leslie D. Alexander、Victoria A. Johnson、Chun-Chieh Lin、Jeremiah Savage、Ricardo Corral、Jason Moss、Tim S. Slugocki、Erinprit K. Singh、Melinda R. Davis、Suchitra Ravula、Jamie E. Spicer、Jenna L. Oelrich、Andrea Thornquist、Chung-Mao Pan、Shelli R. McAlpine

  DOI：10.1016/j.bmc.2010.07.042

  日期：2010.9

  Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative. Published by Elsevier Ltd.
• Synthesis of Second-Generation Sansalvamide A Derivatives: Novel Templates as Potential Antitumor Agents
  作者：Rodrigo A. Rodriguez、Po-Shen Pan、Chung-Mao Pan、Suchitra Ravula、Stephanie Lapera、Erinprit K. Singh、Thomas J. Styers、Joseph D. Brown、Julia Cajica、Emily Parry、Katerina Otrubova、Shelli R. McAlpine

  DOI：10.1021/jo061830j

  日期：2007.3.1

  We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.
• d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study
  作者：Defa Bai、Siming Yu、Shenghui Zhong、Bingxin Zhao、Shaoling Qiu、Jianwei Chen、Jignesh Lunagariya、Xiaojian Liao、Shihai Xu

  DOI：10.3390/ijms18030544

  日期：——

  cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro

  Galaxamide是一种来自Galaxaurafilosa的提取物，是一种含有五种l-亮氨酸的环状五肽。由于特殊的环状结构和优异的抗癌活性，Galaxamide及其类似物的合成及其后续的生物应用引起了极大的关注。在目前的工作中，我们通过用苯丙氨酸代替一个亮氨酸取代了一个L-亮氨酸，并改变了d-氨基酸的位置，从而合成了六个Galaxamide类似物。测试了合成的Galaxamide类似物对四种体外人类癌细胞系，人类肝细胞细胞（HepG2），人类乳腺癌细胞（MCF-7），人类乳腺癌细胞（MDA-MB-435）的抗癌作用。宫颈癌细胞系（Hela）。结果表明，具有不同d-氨基酸位置的Galaxamide类似物显示出独特的抗癌潜力。在位置5（Analog-6）上含有d-氨基酸的Galaxamide类似物具有最强的抗癌活性。机制研究表明，Analog-6可能通过抑制HepG2细胞在细胞周期亚G1期的